Alkynes oxidative reactions

Alkyne oxidation reactions are of little value now but were used bi > tortcally in Uie structure -detemiination of substances isolated fron) nau-ral sources. For example, the location of the triple bond in the chain of tariric acid was established by finding that oxidation with KMnO., gax e dodecar. c add and hexanedioic acid ... 

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

Aikynes undergo a variety of reactions using either Pd(H) or Pd(0), and they are treated separately oxidative reactions of alkynes with Pd(Il) are treated in Chapter 3, Section 8. Pd(0)-catalyzed reactions of alkynes with halides in Section 1.1.2 in this chapter, and other reactions in this section. 

Problem 8.6 What alkyne would you start with to prepare each of the following compounds by a hydroboration/oxidation reaction ... 

The hydration of C-C triple bonds represents one of the most atom economical and environmentally friendly oxidation reactions [37], Recently, Nolan and co-workers reported the cationic [Au(lPr)][SbF ] system, which was generated in situ from [AuCl(lPr)] and AgSbF. The catalyst system showed remarkable activity in the hydration of a large range of alkynes, at An loadings as low as 10 ppm (typically 50-100 ppm), under acid-free conditions (Table 10.6) [38],... 

Heteropoly acids can be synergistically combined with phase-transfer catalysis in the so-called Ishii-Venturello chemistry for oxidation reactions such as oxidation of alcohols, allyl alcohols, alkenes, alkynes, P-unsaturated acids, vic-diols, phenol, and amines with hydrogen peroxide (Mizuno et al., 1994). Recent examples include the epoxidations of alkyl undecylenates (Yadav and Satoskar, 1997) and. styrene (Yadav and Pujari, 2000). 

The anti-Markovnikov product was formed with >95% regioselectivity at 35°C. The examples in Scheme 5-21, Eq. (1) show that cyano and hydroxyl functional groups are tolerated by the catalyst, and diphenylphosphine oxide can be added to both C=C bonds in a di-alkyne. The reaction also worked for internal alkynes (Scheme 5-21, Eq. 2). Unusual Markovnikov selectivity was observed, however, for 1-ethynyl-cyclohexene (Scheme 5-21, Eq. 3) [17]. 

The heterogeneous catalytic system iron phthalocyanine (7) immobilized on silica and tert-butyl hydroperoxide, TBHP, has been proposed for allylic oxidation reactions (10). This catalytic system has shown good activity in the oxidation of 2,3,6-trimethylphenol for the production of 1,4-trimethylbenzoquinone (yield > 80%), a vitamin E precursor (11), and in the oxidation of alkynes and propargylic alcohols to a,p-acetylenic ketones (yields > 60%) (12). A 43% yield of 2-cyclohexen-l-one was obtained (10) over the p-oxo dimeric form of iron tetrasulfophthalocyanine (7a) immobilized on silica using TBHP as oxidant and CH3CN as solvent however, the catalyst deactivated under reaction conditions. 

By far the most commonly used - though not the most environmentally friendly -solvent is CCl (or more usually water-CCl ). In a classic paper Sharpless et al. showed that oxidation reactions of RuO (and other some Ru-based oxidants) were accelerated by addition of a little acetonitrile to the conventional water-CCl biphasic mixture. It was suggested that the CH3CN might function as a mild donor stabilising a lower oxidation state carboxylato Ru species which could be involved in the catalytic process [260]. A comparative study of CCl, acetone, ethyl acetate, cyclohexane and acetone for cleavage of alkenes and alkynes by RuClg/aq. IO(OH)3/solvent showed that cyclohexane was the most effective [216]. Other solvents sometimes... 

There is a rich chemistry of alkene and alkyne oxidation by RuO. The main application lies in alkene cleavage, bnt there is growing interest in cw-dihydroxylation by the reagent. In the sections below we first consider oxidations which do not sever the C=C bond (epoxidation, ctT-dihydroxylation, ketohydroxylation), and then alkene cleavage reactions. 

The key success of these metal-catalyzed processes lies in the replacement of an unachievable carbozincation by an alternative carbometallation involving the transition metal catalyst, or another pathway such as an alkene-alkene (or alkyne) oxidative coupling promoted by a group IV transition metal complex, followed by transmetallation. An organozinc is ultimately produced and the latter can be functionalized by reaction with electrophiles. 

Hypervalent iodine oxidation reactions of unsaturated compounds such as a,/ -unsaturated compounds, alkynes, and silylenol ethers afford the important substructures of several natural products. 

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